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H. Jayaram, S. Singhal, B. Bhatia, P. T. Khaw, G. A. Limb; Taurine and Notch Pathway Inhibition Promote in vitro Differentiation of Adult Human Müller Stem Cells Towards a Photoreceptor Fate. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1280.
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Müller stem cells derived from the adult human retina may constitute a potential source of cells for use in cell-based therapies to treat retinal degenerative diseases. This study investigated the ability of these cells to differentiate towards a photoreceptor fate following culture with factors known to induce changes in gene expression by retinal stem cells.
Cells were cultured in vitro for one week in the presence of taurine or the gamma secretase inhibitor DAPT. Changes in gene expression were studied by RT-PCR using primers for genes known to be involved in photoreceptor differentiation, namely Crx, Nrl and Nr2e3. Cellular morphology in each group was also studied using transmission light microscopy.
Both treatment conditions caused an increase in the expression of markers of photoreceptor progenitors. DAPT treated cells showed a significant upregulation of Crx and Nrl expression after 1 week. Culture of Müller stem cells with taurine for a similar period of time also induced a mild increase in Crx expression with a more significant increase in Nrl expression. Following culture with these factors, changes in cellular morphology towards a neural phenotype were observed, with elongated processes and secondary and tertiary branching.
It has been shown that retinal progenitors expressing Nrl during development are ontogenetically ideal to replace photoreceptors in experimental models of photoreceptor cell death. The observations that taurine and DAPT treatment promote differentiation of Müller stem cells towards a photoreceptor fate in vitro suggest that these cells have the ability to differentiate into an ontogenic state suitable for transplantation to restore photoreceptor cell function lost by retinal disease.
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